scholarly journals Immunomodulatory drug therapy for the disease caused by SARS-CoV-2 infection (COVID-19)

2020 ◽  
Vol 48 ◽  
pp. 51-67
Author(s):  
D. E. Karateev ◽  
E. L. Luchikhina
Keyword(s):  
Immunosuppressive Therapy ◽  
Interleukin 6 ◽  
Interleukin 1 ◽  
Evidence Base ◽  
Multiple Organ ◽  
Janus Kinase ◽  
High Dose ◽  
Jak Inhibitors ◽  
Interleukin 6 Receptor ◽  
Novel Coronavirus

This systematic review focuses on the state-of-the-art pharmacotherapy of immune disorders in the novel coronavirus infection (COVID-19), leading to a cytokine storm and uncontrolled inflammatory response that causes severe tissue damage and multiple organ failure. A lot of theoretical, experimental and clinical data support the need for immunomodulatory (immunosuppressive) therapy for this disease. It should be emphasized that all immunomodulatory drugs for COVID-19 are prescribed off label, and the evidence base of the results of randomized trials is just being accumulated. We review the immunomodulatory therapy for COVID-19 with the following agents: glucocorticoids, hydroxychloroquine and chloro-quine, type 1 interferons, interleukin-6 antagonists (tocilizumab, sarilumab, olokizumab), interleukin-1 p inhibitor canakinumab, tumour necrosis factor inhibitors (infliximab), Janus kinase (JAK) inhibitors (tofacitinib, baricitinib, ruxolitinib), as well as drugs with other mechanisms of action (abatacept, nivolumab, tacrolimus, sirolimus, fingolimod, melphalan, cyclosporine, methotrexate). At the moment, the most reasonable is the use of interleukin-6 receptor inhibitors, intermediate and high dose glucocorticoids, and JAK inhibitors. Based on the latest data from clinical studies, especially the "Solidarity” trial, the use of hydroxychloroquine and chloroquine seems to have insufficient evidence. There are significant pathophysiological overlaps in the development of immunopathology in COVID-19 and in rheumatic diseases, and the strategy of early aggressive immunosuppressive therapy proposed by a number of researchers almost completely coincides with the current strategies for rheumatoid arthritis.

scholarly journals Expression of Cytokines and Cytokine Receptors-Genes in Patients with Different Forms of Thyroid Pathology in Ukrainian Population

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Iryna Kamyshna ◽  
Aleksandr Kamyshnyi
Keyword(s):  
Autoimmune Thyroiditis ◽  
Interleukin 6 ◽  
Interleukin 1 ◽  
White Blood Cells ◽  
Elevated Serum ◽  
Interleukin 10 ◽  
Thyroid Peroxidase ◽  
Thyroid Peroxidase Antibodies ◽  
Interleukin 6 Receptor ◽  
Peripheral White Blood Cells

Abstract Multiple susceptibility genes can be involved in the development of Hashimoto’s thyroiditis. Some of these genes are implicated in other autoimmune diseases, while others are specific to thyroid autoimmune response. 153 patients with thyroid pathology were enrolled in the study (152 women and 1 man, the average age was 46,02±14,3). They were divided into 3 groups: 16 patients with postoperative hypothyroidism; 65 patients with hypothyroidism resulting from autoimmune thyroiditis, and 72 patients with both AIT and elevated serum an anti-thyroglobulin and anti-thyroid peroxidase antibodies. We used a pathway-specific real-time Polymerase chain reaction array to identify and verify cytokines and receptor pathway-associated gene expression in peripheral white blood cells in randomly selected 12 individuals from each group. In the patients with postoperative hypothyroidism and those with hypothyroidism resulting from autoimmune thyroiditis, the expression of Chemokine (C-X3-C motif) receptor 1, Chemokine (C-X-C motif) receptor 4, Interleukin 6, and Interleukin 6 receptor significantly decreased, while the expression of IL6ST and IL10RA increased. In contrast, mRNA levels of Chemokine (C-X3-C motif) receptor 1, Chemokine (C-X-C motif) receptor 4, Interleukin 6, and Interleukin 6 receptor increased in the autoimmune thyroiditis patients with elevated serum anti-thyroglobulin and anti-thyroid peroxidase antibodies, while the expression of Interleukin 6 signal transducer and Interleukin 10 receptor, alpha decreased in this group of patients. The patients with hypothyroidism resulting from autoimmune thyroiditis and patients with elevated serum anti-thyroglobulin and anti-thyroid peroxidase antibodies had significantly lowered expression of Interleukin 10, while the expression of Interleukin 1, beta and Interleukin 1 receptor, type I was elevated. autoimmune thyroiditis and hypothyroidism affect the mRNA-level expression of cytokines and cytokine receptor genes in a gene-specific manner, and these changes to gene expression can be among the triggers of autoimmune inflammation progression in the thyroid gland. Transcriptional activity of cytokines, inducer, and receptor genes in the peripheral white blood cells can be used as an important minimally invasive prognostic marker of the autoimmune thyroid disease severity.

Inflammatory cytokines in pediatric cardiac surgery and variable effect of the hemofiltration process

Perfusion ◽  
2005 ◽  
Vol 20 (5) ◽  
pp. 263-268 ◽  
Author(s):  
Gianluca Brancaccio ◽  
Emmanuel Villa ◽  
Elia Girolami ◽  
Guido Michielon ◽  
Cristiana Feltri ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Interleukin 6 ◽  
Multiorgan Failure ◽  
Interleukin 1 ◽  
Clinical Status ◽  
Anesthesia Induction ◽  
Variable Effect ◽  
Anesthetic Drugs ◽  
Tnf Α ◽  
Interleukin 6 Receptor

Cardiac surgery with cardiopulmonary bypass (CPB) elicits an inflammatory response and has a multitude of biological consequences, ranging from subclinical organ dysfunction to severe multiorgan failure. Pediatric patients are more prone to have a reaction that can jeopardize their outcome. Cytokines are supposed to be important mediators in this response: limiting their circulating levels is, therefore, appealing. We investigated the pattern of cytokine release during pediatric operation for congenital heart anomalies in 20 patients, and the effect of hemofiltration. Tumor necrosis factor a (TNF-α) was elevated after anesthesia induction and showed significant decrease during CPB. Hemofiltration reduced its concentration, but the effect disappeared on the following day. Interleukin-1 (IL-1) increased slowly at the end of CPB and hemofiltration had no effect. Interleukin-6 (IL-6) showed a tendency toward augmentation during rewarming and hemofiltration did not significantly affect the course. Soluble interleukin-6 receptor (sIL-6r) had a pattern similar to TNF-α, but hemofiltration had no effect. On the other hand, interleukin-8 (IL-8) behaved like IL-6. Our findings suggest that baseline clinical status, anesthetic drugs, and maneuvers before incision may elicit a cytokine response, whereas rewarming is a critical phase of CPB. Hemofiltration is effective in removal of TNF-α, but its role is debatable for the control of IL-1, IL-6, sIL-6r and IL-8 levels.

scholarly journals Interleukin-6 Blockade With Tocilizumab in Anakinra-Refractory Febrile Infection-Related Epilepsy Syndrome (FIRES)

2020 ◽  
Vol 7 ◽  
pp. 2329048X2097925
Author(s):  
Coral M. Stredny ◽  
Siobhan Case ◽  
Arnold J. Sansevere ◽  
MaryBeth Son ◽  
Lauren Henderson ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Interleukin 6 ◽  
Interleukin 1 ◽  
Refractory Status Epilepticus ◽  
Cognitive Outcomes ◽  
Epilepsy Syndrome ◽  
Immune System Dysfunction ◽  
Interleukin 6 Receptor ◽  
Pro Inflammatory Cytokines ◽  
New Onset

Febrile infection-related epilepsy syndrome (FIRES) is characterized by new onset refractory status epilepticus in a previously healthy child that is associated with poor cognitive outcomes and chronic epilepsy. Innate immune system dysfunction is hypothesized to be a key etiologic contributor, with a potential role for immunotherapy blocking pro-inflammatory cytokines, such as interleukin-1β and interleukin-6. We present a case of FIRES refractory to anakinra, an interleukin-1 receptor antagonist, subsequently treated with the ketogenic diet and tocilizumab, an interleukin-6 receptor antagonist, temporally associated with seizure cessation and a favorable 1-year outcome.

scholarly journals Janus kinase inhibitors for the treatment of rheumatoid arthritis

2021 ◽  
Vol 64 (2) ◽  
pp. 105-108
Author(s):  
Sun Hee Jang ◽  
Ji Hyeon Ju
Keyword(s):  
Rheumatoid Arthritis ◽  
Kinase Inhibitors ◽  
Interleukin 1 ◽  
Janus Kinase ◽  
Jak Inhibitor ◽  
Jak Inhibitors ◽  
Biologic Dmards ◽  
Signal Transducers ◽  
Refractory Rheumatoid Arthritis ◽  
Stat Signaling

Rheumatoid arthritis is a chronic inflammatory destructive disorder that affects the joints, muscles, and tendons accompanying various extra-articular manifestations. Traditional disease-modifying anti-rheumatic drugs (DMARDs) represent the basic treatment for rheumatoid arthritis. Over the last 20 years, biologic DMARDs (tumor necrosis factor inhibitors, interleukin-1 inhibitors, interleukin-6 inhibitors, T cell inhibitors, and B cell inhibitors) have been widely used as a novel class of DMARDs that have efficacy and efficiency. Discovery of the underlying pathogenesis of autoimmune disease enables us to develop new target therapies such as a Janus kinase (JAK) inhibitor. Activated JAK is known to activate signal transducers as well as activators of transcription (STAT) signaling. A JAK inhibitor is a type of medication that functions by inhibiting the JAK-STAT signaling pathway. In addition, it is easy to take a JAK inhibitor orally. In Korea, several JAK inhibitors have been approved. This review describes the types of JAK inhibitors, recommended doses, side effects, and updated European Alliance of Associations for Rheumatology guidelines. Clinicians should more often consider JAK inhibitors in the treatment of refractory rheumatoid arthritis in current rheumatology clinics

scholarly journals Characteristics of complex therapy of immuno-inflammatory rheumatic diseases in COVID-19 pandemic conditions

2021 ◽  
Vol 5 (5) ◽  
pp. 260-267
Author(s):  
R.R. Samigullina ◽  
◽  
V.I. Mazurov ◽  
E.A. Trofimov ◽  
◽  
...  
Keyword(s):  
Multiple Organ Failure ◽  
Organ Failure ◽  
Rheumatic Diseases ◽  
Interleukin 6 ◽  
Multiple Organ ◽  
Genetically Engineered ◽  
High Dose ◽  
Inflammatory Rheumatic Diseases ◽  
Cytokine Storm ◽  
Complex Therapy

The rapid spread of a new coronavirus infection (COVID-19) requires innovative solutions, including tactics optimization in using genetically engineered and targeted drugs in patients with immuno-inflammatory rheumatic diseases (RD). The authors studied the characteristics of the complex therapy of immuno-inflammatory RD in the COVID-19 pandemic conditions, analyzed the COVID-19 course in patients with RD who received combined therapy with genetically engineered and basic synthetic anti-rheumatic drugs and were under follow-up from March 2020 to March 2021. The researchers found that synthetic basic (methotrexate, leflunomide, etc.), targeted synthetic (tofacitinib, baricitinib, apremilast) and biologic disease-modifying antirheumatic drugs used in the RD treatment, except high-dose glucocorticoids and anti-B cell drugs (rituximab), do not have a negative effect and are not associated with a severe COVID-19 course. The use of interleukin-6 (IL-6) inhibitors is the standard pathogenetic therapy for cytokine release syndrome in COVID-19. Proactive therapy with IL-6 inhibitors provides inhibition of systemic inflammation and contributes to the suppression of cytokine storm syndrome, preventing the development of multiple organ failure and fatal outcome. KEYWORDS: rheumatic diseases, cytokine storm, multiple organ failure, genetically engineered biological drugs, interleukin-6, COVID-19. FOR CITATION: Samigullina R.R., Mazurov V.I., Trofimov E.A. Characteristics of complex therapy of immuno-inflammatory rheumatic diseases in COVID-19 pandemic conditions. Russian Medical Inquiry. 2021;5(5):260–267 (in Russ.). DOI: 10.32364/2587-6821-2021- 5-5-260-267.

scholarly journals Clinical characteristics and outcomes of critically ill mechanically ventilated COVID-19 patients receiving interleukin-6 receptor antagonists and corticosteroid therapy: a preliminary report from a multinational registry

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Marwa Amer ◽  
Ahmed M. Kamel ◽  
Mohammed Bawazeer ◽  
Khalid Maghrabi ◽  
Abid Butt ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Critically Ill ◽  
Interleukin 6 ◽  
Preliminary Report ◽  
Clinical Characteristics ◽  
Dose Range ◽  
Prescribing Patterns ◽  
High Dose ◽  
Receptor Antagonists ◽  
Interleukin 6 Receptor

Abstract Background Interleukin-6 receptor antagonists (IL-6RAs) and steroids are emerging immunomodulatory therapies for severe and critical coronavirus disease (COVID-19). In this preliminary report, we aim to describe the epidemiology, clinical characteristics, and outcomes of adult critically ill COVID-19 patients, requiring invasive mechanical ventilation (iMV), and receiving IL-6RA and steroids therapy over the last 11 months. Materials and methods International, multicenter, cohort study derived from Viral Infection and Respiratory Illness University Study registry and conducted through Discovery Network, Society of Critical Care Medicine. Data were collected between March 01, 2020, and January 10, 2021. Results Of 860 patients who met eligibility criteria, 589 received steroids, 170 IL-6RAs, and 101 combinations. Patients who received IL-6RAs were younger (median age of 57.5 years vs. 61.1 and 61.8 years in the steroids and combination groups, respectively). The median C-reactive protein level was > 75 mg/L, indicating a hyperinflammatory phenotype. The median daily steroid dose was 7.5 mg dexamethasone or equivalent (interquartile range: 6–14 mg); 80.8% and 19.2% received low-dose and high-dose steroids, respectively. Of the patients who received IL-6RAs, the majority received one dose of tocilizumab and sarilumab (dose range of 600–800 mg for tocilizumab and 200–400 mg for sarilumab). Regarding the timing of administration, we observed that steroid and IL-6RA administration on day 0 of ICU admission was only 55.6% and 39.5%, respectively. By day 28, when compared with steroid use alone, IL-6RA use was associated with an adjusted incidence rate ratio (aIRR) of 1.12 (95% confidence interval [CI] 0.88, 1.4) for ventilator-free days, while combination therapy was associated with an aIRR of 0.83 (95% CI 0.6, 1.14). IL-6RA use was associated with an adjusted odds ratio (aOR) of 0.68 (95% CI 0.44, 1.07) for the 28-day mortality rate, while combination therapy was associated with an aOR of 1.07 (95% CI 0.67, 1.70). Liver dysfunction was higher in IL-6RA group (p = 0.04), while the bacteremia rate did not differ among groups. Conclusions Discordance was observed between the registry utilization patterns (i.e., timing of steroids and IL-6RA administration) and new evidence from the recent randomized controlled trials and guideline recommendations. These data will help us to identify areas of improvement in prescribing patterns and enhance our understanding of IL-6RA safety with different steroid regimens. Further studies are needed to evaluate the drivers of hospital-level variation and their impact on clinical outcomes. Trial registration ClinicalTrials.gov: NCT04486521. Registered on July 2020

scholarly journals Anti–Interleukin-6 and Janus Kinase Inhibitors for Severe Neurologic Toxicity of Checkpoint Inhibitors

2021 ◽  
Vol 8 (6) ◽  
pp. e1073
Author(s):  
Alberto Picca ◽  
Nefeli Valyraki ◽  
Cristina Birzu ◽  
Nora Kramkimel ◽  
Olivier Hermine ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Transverse Myelitis ◽  
Janus Kinase ◽  
High Dose ◽  
Janus Kinase Inhibitors ◽  
Biological Responses ◽  
Spine Mri

Background and ObjectivesTo describe the marked clinical and biological responses of a targeted treatment with anti–interleukin-6 (IL-6)–receptor antibody and Janus kinase (JAK) inhibitors in a patient with a severe, corticoresistant CNS toxicity of immune-checkpoint inhibitor (ICI) therapy.MethodsA 58-year-old man was admitted for subacute paraparesis, urinary retention, and ascending paresthesia. He was under treatment with ipilimumab and nivolumab for metastatic melanoma. Spine MRI disclosed multiple T2-hyperintense, contrast-enhancing longitudinally extensive lesions. A diagnosis of ICI-related acute transverse myelitis was made.ResultsICIs were immediately discontinued, and the patient received high-dose glucocorticoids plus 1 session of plasma exchange, but he did not improve. Based on the marked elevation of CSF IL-6 (505 pg/mL), a second-line targeted therapy with anti-IL-6-receptor tocilizumab (8 mg/kg/mo for 3 infusions) plus JAK inhibitor ruxolitinib (50 mg/d) was administered. Patient neurologic status started to improve shortly after, with corresponding radiologic resolution. At 9 months, the patient was able to walk independently, presenting only slight residual disability while remaining in oncologic partial response.DiscussionOur case suggests that some patients with severe, corticoresistant CNS immune-related toxicities of ICIs may benefit from cytokine blockade. Cytokine measurement in serum and CSF might help in selecting patients for personalized treatment strategies.

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